Structural basis for the enhancement of virulence by viral spindles and their in vivo crystallization

Elaine Chiu, Marcel Hijnen, Richard D Bunker, Marion Boudes, Chitra Rajendran, Kaheina Aizel, Vincent Olieric, Clemens Schulze-Briese, Wataru Mitsuhashi, Vivienne Young, Vernon K Ward, Max Bergoin, Peter Metcalf, Fasseli J Coulibaly

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The great benefits that chemical pesticides have brought to agriculture are partly offset by widespread environmental damage to nontarget species and threats to human health. Microbial bioinsecticides are considered safe and highly specific alternatives but generally lack potency. Spindles produced by insect poxviruses are crystals of the fusolin protein that considerably boost not only the virulence of these viruses but also, in cofeeding experiments, the insecticidal activity of unrelated pathogens. However, the mechanisms by which spindles assemble into ultra-stable crystals and enhance virulence are unknown. Here we describe the structure of viral spindles determined by X-ray microcrystallography from in vivo crystals purified from infected insects. We found that a C-terminal molecular arm of fusolin mediates the assembly of a globular domain, which has the hallmarks of lytic polysaccharide monooxygenases of chitinovorous bacteria. Explaining their unique stability, a 3D network of disulfide bonds between fusolin dimers covalently crosslinks the entire crystalline matrix of spindles. However, upon ingestion by a new host, removal of the molecular arm abolishes this stabilizing network leading to the dissolution of spindles. The released monooxygenase domain is then free to disrupt the chitin-rich peritrophic matrix that protects insects against oral infections. The mode of action revealed here may guide the design of potent spindles as synergetic additives to bioinsecticides.
Original languageEnglish
Pages (from-to)3973 - 3978
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume112
Issue number13
DOIs
Publication statusPublished - 2015

Cite this

Chiu, Elaine ; Hijnen, Marcel ; Bunker, Richard D ; Boudes, Marion ; Rajendran, Chitra ; Aizel, Kaheina ; Olieric, Vincent ; Schulze-Briese, Clemens ; Mitsuhashi, Wataru ; Young, Vivienne ; Ward, Vernon K ; Bergoin, Max ; Metcalf, Peter ; Coulibaly, Fasseli J. / Structural basis for the enhancement of virulence by viral spindles and their in vivo crystallization. In: Proceedings of the National Academy of Sciences. 2015 ; Vol. 112, No. 13. pp. 3973 - 3978.
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abstract = "The great benefits that chemical pesticides have brought to agriculture are partly offset by widespread environmental damage to nontarget species and threats to human health. Microbial bioinsecticides are considered safe and highly specific alternatives but generally lack potency. Spindles produced by insect poxviruses are crystals of the fusolin protein that considerably boost not only the virulence of these viruses but also, in cofeeding experiments, the insecticidal activity of unrelated pathogens. However, the mechanisms by which spindles assemble into ultra-stable crystals and enhance virulence are unknown. Here we describe the structure of viral spindles determined by X-ray microcrystallography from in vivo crystals purified from infected insects. We found that a C-terminal molecular arm of fusolin mediates the assembly of a globular domain, which has the hallmarks of lytic polysaccharide monooxygenases of chitinovorous bacteria. Explaining their unique stability, a 3D network of disulfide bonds between fusolin dimers covalently crosslinks the entire crystalline matrix of spindles. However, upon ingestion by a new host, removal of the molecular arm abolishes this stabilizing network leading to the dissolution of spindles. The released monooxygenase domain is then free to disrupt the chitin-rich peritrophic matrix that protects insects against oral infections. The mode of action revealed here may guide the design of potent spindles as synergetic additives to bioinsecticides.",
author = "Elaine Chiu and Marcel Hijnen and Bunker, {Richard D} and Marion Boudes and Chitra Rajendran and Kaheina Aizel and Vincent Olieric and Clemens Schulze-Briese and Wataru Mitsuhashi and Vivienne Young and Ward, {Vernon K} and Max Bergoin and Peter Metcalf and Coulibaly, {Fasseli J}",
year = "2015",
doi = "10.1073/pnas.1418798112",
language = "English",
volume = "112",
pages = "3973 -- 3978",
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Chiu, E, Hijnen, M, Bunker, RD, Boudes, M, Rajendran, C, Aizel, K, Olieric, V, Schulze-Briese, C, Mitsuhashi, W, Young, V, Ward, VK, Bergoin, M, Metcalf, P & Coulibaly, FJ 2015, 'Structural basis for the enhancement of virulence by viral spindles and their in vivo crystallization' Proceedings of the National Academy of Sciences, vol. 112, no. 13, pp. 3973 - 3978. https://doi.org/10.1073/pnas.1418798112

Structural basis for the enhancement of virulence by viral spindles and their in vivo crystallization. / Chiu, Elaine; Hijnen, Marcel; Bunker, Richard D; Boudes, Marion; Rajendran, Chitra; Aizel, Kaheina; Olieric, Vincent; Schulze-Briese, Clemens; Mitsuhashi, Wataru; Young, Vivienne; Ward, Vernon K; Bergoin, Max; Metcalf, Peter; Coulibaly, Fasseli J.

In: Proceedings of the National Academy of Sciences, Vol. 112, No. 13, 2015, p. 3973 - 3978.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structural basis for the enhancement of virulence by viral spindles and their in vivo crystallization

AU - Chiu, Elaine

AU - Hijnen, Marcel

AU - Bunker, Richard D

AU - Boudes, Marion

AU - Rajendran, Chitra

AU - Aizel, Kaheina

AU - Olieric, Vincent

AU - Schulze-Briese, Clemens

AU - Mitsuhashi, Wataru

AU - Young, Vivienne

AU - Ward, Vernon K

AU - Bergoin, Max

AU - Metcalf, Peter

AU - Coulibaly, Fasseli J

PY - 2015

Y1 - 2015

N2 - The great benefits that chemical pesticides have brought to agriculture are partly offset by widespread environmental damage to nontarget species and threats to human health. Microbial bioinsecticides are considered safe and highly specific alternatives but generally lack potency. Spindles produced by insect poxviruses are crystals of the fusolin protein that considerably boost not only the virulence of these viruses but also, in cofeeding experiments, the insecticidal activity of unrelated pathogens. However, the mechanisms by which spindles assemble into ultra-stable crystals and enhance virulence are unknown. Here we describe the structure of viral spindles determined by X-ray microcrystallography from in vivo crystals purified from infected insects. We found that a C-terminal molecular arm of fusolin mediates the assembly of a globular domain, which has the hallmarks of lytic polysaccharide monooxygenases of chitinovorous bacteria. Explaining their unique stability, a 3D network of disulfide bonds between fusolin dimers covalently crosslinks the entire crystalline matrix of spindles. However, upon ingestion by a new host, removal of the molecular arm abolishes this stabilizing network leading to the dissolution of spindles. The released monooxygenase domain is then free to disrupt the chitin-rich peritrophic matrix that protects insects against oral infections. The mode of action revealed here may guide the design of potent spindles as synergetic additives to bioinsecticides.

AB - The great benefits that chemical pesticides have brought to agriculture are partly offset by widespread environmental damage to nontarget species and threats to human health. Microbial bioinsecticides are considered safe and highly specific alternatives but generally lack potency. Spindles produced by insect poxviruses are crystals of the fusolin protein that considerably boost not only the virulence of these viruses but also, in cofeeding experiments, the insecticidal activity of unrelated pathogens. However, the mechanisms by which spindles assemble into ultra-stable crystals and enhance virulence are unknown. Here we describe the structure of viral spindles determined by X-ray microcrystallography from in vivo crystals purified from infected insects. We found that a C-terminal molecular arm of fusolin mediates the assembly of a globular domain, which has the hallmarks of lytic polysaccharide monooxygenases of chitinovorous bacteria. Explaining their unique stability, a 3D network of disulfide bonds between fusolin dimers covalently crosslinks the entire crystalline matrix of spindles. However, upon ingestion by a new host, removal of the molecular arm abolishes this stabilizing network leading to the dissolution of spindles. The released monooxygenase domain is then free to disrupt the chitin-rich peritrophic matrix that protects insects against oral infections. The mode of action revealed here may guide the design of potent spindles as synergetic additives to bioinsecticides.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386404/pdf/pnas.201418798.pdf

U2 - 10.1073/pnas.1418798112

DO - 10.1073/pnas.1418798112

M3 - Article

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SP - 3973

EP - 3978

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -